Post on 27-Jun-2015
description
G1HB - Hart & Bloedsomloop - April 2012
Cardiac mechanics
Paul Steendijk, PhD
Associate Professor Cardiovascular PhysiologyDepartment of Cardiology, LUMC
p.steendijk@lumc.nl
Determinants of cardiac performance
• Myocardial contractility (inotropy & lusitropy)- contraction, relaxation
• Loading conditions- preload, afterload, geometry
• Chronotropy- heart rate
• Temporal and spatial (non)-uniformity- dyssynchrony
Stiffness (Elastance) = dP/dVCompliance = dV/dP
Intrinsic propertiesby load-independent characterization
early compartmentlate compartmentdt = 0.010 s
0.0
1.0
2.0
3.0
0.0 0.2 0.4 0.6 0.8 1.0
Time (s)
Ela
stan
ce (
mm
Hg/
mL)
0.0
1.0
2.0
3.0
0 0.2 0.4 0.6 0.8 1
0
50
100
150
200
0 50 100 150 200 250
Volume (mL)
Pre
ssu
re (
mm
Hg
)
t=0.00
t=0.02
t=0.04
t=0.06
t=0.08
t=0.10
t=0.14
t=0.18
t=0.22
t=0.30
Time-varying elastance (stiffness)
Senzaki, Circulation 1996
Reduced cardiac output (stroke volume)
increased afterloadreduced preload
reduced contractility reduced
compliance
Effects of load changes(preload, afterload)
Pre
ssu
re
Volume
Preload change Afterload change
Volume
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
Systolic vs. Diastolic Heart Failure
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
0
20
40
60
80
100
120
0 30 60 90 120 150
Pre
ssu
re
Volume
Systolic Heart Failure Diastolic Heart Failure
Volume
Systolic and diastolic PV relationsDobutamine vs. Baseline
0
25
50
75
100
125
0 50 100 150LV Volume (ml)
LV P
ress
ure
(m
mH
g)
BaselineDobutamine
Steendijk et al. J Am Coll Cardiol 1998; 32: 816-26
2.2: Contraction mechanisms
2.3:Excitation-contraction coupling
2.4: Pump function
G1HB - Hart & Bloedsomloop - April 2012
Cardiac mechanics
Cross-bridge cycling & calcium
Calcium & cross-bridge cycling
Calcium concentrationsExtracellular Ca concentration: [Ca]o ~ 1.2 mM (1200 μM) Intracellular Ca concentration: [Ca]i ~ 100 nM (0.1 μM)- 104-fold concentration gradient
During action potential:- Ca enters via L-type Ca channels- Free [Ca]i increases ~10-fold
[Ca]o , [Ca]i and Force
- [Ca]i depends on [Ca]o
- Developed force is dependent on free [Ca]i
Calcium-induced calcium release from SR- Ca influx is not sufficient to raise [Ca]i and initiate contraction- Sarcoplasmic reticulum stores large amounts of Ca- Ca entry (L-type Ca channels) triggers Ca release from SR via Ryanodine receptors
Calcium re-uptake into the SR- Ca is sequestered into SR by SERCA pump (SR Ca-ATPase)- Phospholamban regulates SERCA; phosphorylation removes its inhibitory effect- Calsequestrin is a SR Ca-binding protein
Calcium removal initiates relaxation
Species differences: Humans ≈ Rabbit
- Ca must be removed from the cytosol to lower [Ca]i and allow relaxation- Routes: SERCA (SR-ATPase), Na/Ca exchange (NCX), SL-ATPase
Cave:Na (“natrium”) = SodiumK (“kalium”) = Potassium
Calcium handling
Beta-receptor stimulation & ECC- Sympathetic activation >> release norepinephrine >> stimulate beta- receptors on SL >> stimulates cAMP production >> protein kinase A- Phosphorylation of L-type Ca-channels: positive inotropic effect (improves contraction)- Phosphorylation of phospholamban (PLB) and troponin-I (TnI): positive lusitropic effect (improves relaxation)
- Myofilaments (Actine-Myosine)- Myofibrils- Mitochondria (ATP)
-Sarcolemma, T-tubule- Sarcoplasmic reticulum- Cisterna
Anatomy & E-C coupling
Sarcomere length and intracellular calcium control force
Isometric force is increased by:
Increased intracellular calcium- binding to Tn-C >> actine-myosin interaction
Increased sarcomere length(“Starling’s Law of the Heart”)- Optimal actine-myosine overlap- Reduced lattice spacing- Altered myosin head orientation
Interaction of two mechanisms- Increased calcium sensitivity at increased sarcomere length
Mechanical dyssynchrony (Heart failure and LBBB)Cardiac Resynchronization Therapy (CRT)
0
20
40
60
80
100
120
140 160 180 200 220
LV Volume (ml)
LV P
ress
ure
(m
mH
g)
Baseline
LV 120
BiV 120
Steendijk et al. Eur Heart J Suppl 2004; 6: D35-42
Cardiac Resynchronization Therapy (CRT)Acute effects
Nelson et al., Circulation 2000
Myocardial Oxygen Consumption (MVO2)LV Pacing vs. Dobutamine
Steendijk et al. Circulation 2006; 113: 1295-1304
Cessation of biventricular pacingafter 6 months of CRT
Asynchronous mechanical activation
McVeigh, Magn Res Med 1998